: For ethical and economic reasons, many Phase III cancer clinical trials incorporate group sequential interim monitoring to permit appropriate early stopping in the presence of a clear treatment effect. Frequently, staggered entry of patients into these studies is an operational necessity which can complicate the distributional properties of the test statistics used. This difficulty is exacerbated when multiple outcome are being considered, especially if one or more of the outcomes is a failure time. However, a number of significant advances in survival analysis theory and implementation over the last several decades have resulted in a rich variety of statistics which can be sensitive to many different alternative hypotheses: but the flexibility and applicability to the group sequential setting is severely limited by the analytic complexity of the underlying distributions. The proposed research will seek to address these issues through the following interrelated goals: (1) Develop flexible Monte Carlo methods for accurately determining the null distribution of multivariate statistical tests in a group sequential clinical trial with staggered entry of patients; (2) Develop versatile survival analysis test procedures possessing improved flexibility, which can be generalized to permit tied data, stratification, and the comparison of more than two treatments; (3) Evaluate and compare these versatile procedures using analytic, data, and simulation studies so that clear criteria for optimal use can be established; (4) Further extend these results for evaluating power and sample size requirements in group sequential designs; (5) Use these Monte Carlo procedures to construct flexible multivariate group sequential boundaries which correspond to hypotheses which are clinically relevant; (6) Develop a suitable method of assessing multivariate information accrual so that the alpha-spending approach for designing sequential clinical trials can be applied to this setting; and (7) Implement these methods in flexible, well documented, and user-friendly software. The theme for this research is increasing appropriate utilization of multiple endpoint data in cancer clinical trials through development of flexible multivariate test statistics in a group sequential setting.